It has long been known that certain natural biologically active substances can be obtained from the glands of animals and the substances so obtained utilized in the treatment of deficiencies of the human body. One such substance is the adrenocorticotropic hormone, commonly called ACTH, which for many years has been obtained from the pituitary glands of animals, particularly porcine and bovine pituitary glands.
The burden of having to collect the relatively small pituitary glands of animals at the time the animals are slaughtered, the limitation to the quantity of such glands which can be collected and the extensive purification procedures which are required to produce peptides which can be administered to humans, are indeed formidable disadvantages to the preparation of natural peptide hormones from animal glands. For many years the art has eagerly awaited the discovery of practical methods and compounds which enable the commercial synthesis of such peptides as ACTH from other than animal sources. To our knowledge there have been no such compounds or methods prior to the discoveries of the present invention.
The human adrenocorticotropic hormone (ACTH) has been identified as having the following structure: ##STR1## where the abbreviations Phe, Glu, Leu, etc. stand for the different amino acid groupings in the peptide chain and the numbers represent the positions of the amino acid groups in the chain according to accepted nomenclature. See the article by Riniker et al, in Nature New Biology, 235, 114-115, (1972).
It is a principal object of this invention to discover intermediate resin peptides from which biologically active peptides may be derived, particularly peptides with adrenocorticotropic hormone activity, and to provide effective processes for the commercial production of such peptides. Other more specific objects will become apparent as this specification proceeds.
We are aware of disclosures of certain laboratory methods for the synthesis of certain peptides of relatively short amino chain lengths. These include an article by R. B. Merrifield entitled "Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide" at pages 2149 to 2154 in Vol. 85 of Journal of the American Chemical Society (1963) and a book entitled "Solid Phase Peptide Synthesis" by John W. Stewart and Janis D. Young published by W. H. Freeeman and Company of San Francisco, California, but find in these publications no disclosures of resin peptides having amino groups of the kind and in the sequence involved in the present invention.